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Clever chemistry and a new class of antibiotics

January 21, 2014
A more rigid key in the lock

Researchers at Brown and MIT re-engineered some acyldepsipeptides — ADEPs — to make them more rigid and better able to disrupt the biochemistry of bacteria. The changes vastly increased potency of ADEPs. Credit: Sello lab/Brown University

A new class of molecules called acyldepsipeptides — ADEPs — may provide a new way to attack bacteria that have developed resistance to antibiotics. Researchers at Brown and MIT, including Chemistry graduate student Daniel Carney, have discovered a way to increase the potency of ADEPs by up to 1,200 times. Their findings appear in the Journal of the American Chemical Society.

Now, researchers from Brown University and the Massachusetts Institute of Technology have shown that giving the ADEPs more backbone can dramatically increase their biological potency. By modifying the structure of the ADEPs in ways that make them more rigid, the team prepared new ADEP analogs that are up to 1,200 times more potent than the naturally occurring molecule.

“The work is significant because we have outlined and validated a strategy for the enhancing the potency of this promising class of antibacterial drug leads,” said Jason Sello, professor of chemistry at Brown and the paper’s senior author. “The molecules that we have synthesized are among the most potent antibacterial agents ever reported in the literature.”

Read more of Kevin Stacey's article about the new class of molecules.